Methods are already known in which a supercritical fluid is used as an anti-solvent to precipitate particles of a substance of interest from solution or suspension. One such method is known as “SEDS”™ (“Solution Enhanced Dispersion by Supercritical fluids”) and is disclosed in WO-95/01221. In SEDS™, a target substance is dissolved or suspended in an appropriate vehicle, and the solution or suspension then co-introduced into a particle formation vessel with a supercritical anti-solvent fluid in which the vehicle is soluble. The co-introduction is effected in a particular way, to ensure that:
both the solution/suspension and the supercritical fluid enter the vessel at substantially the same point, which is also the same or substantially the same as the point where they meet; and
in the region where the fluids meet and enter the vessel, the mechanical energy of the supercritical fluid serves to disperse the solution/suspension (ie, to break it up into individual fluid elements) at the same time as the supercritical fluid extracts the vehicle so as to cause particle formation.
Thus, in SEDS ™, the supercritical fluid eves not only as an anti-solvent but also as a mechanical dispersing agent. The simultaneity of fluid contact, dispersion and particle formation provides a high degree of control over the physicochemical properties of the particulate product.
One particular embodiment of SEDS™ is described in WO-96/00610. The target substance is dissolved or suspended in a first vehicle, and the solution/suspension is then contacted, either at or immediately prior to its contact with the co-introduced anti-solvent, with a second vehicle. The second vehicle must be soluble in the anti-solvent but the first need not be, since both vehicles are extracted together into the anti-solvent. This embodiment widens the applicability of the basic SEDS™ technique to further target substances and vehicles: a first vehicle may be used which would not otherwise be extractable into the chosen and-solvent but which is compatible with the target substance, and a second vehicle may be used which, although enable into the anti-solvent, is less compatible with the target substance.
The method disclosed in WO-96/00610 requires the first and second vehicles to be miscible with one another, preferably in all proportions. This naturally constrains the choice of vehicle pairs available for use with any given target substance and anti-solvent.
The present invention aims to provide an alternative method for particle formation, embodiments of which can be used to widen the choice of useable target substance/vehicle/anti-solvent combinations.